The objective is to define central effects of a narcotic antagonist (naltrexone) and of methadone in man. The methods include electroencephalography, auditory evoked potentials, Contingent Negative Variation, performance on an auditory detection task (including reaction time) pupillography, respiratory rate, heart rate, and questionnaires for the assessment of subjective effects of opiates. Plasma, urine and fecal levels of methadone, naltrexone and its metabolites are determined in conjunction with the physiological and psychological measurements. The effects of methadone were assessed in twelve hospitalized patients; half of them were built up to 80 milligrams/day, the other half to 40 milligrams/day. Repeated measures during the build-up and the stabilization period defined differences between the two dosage schedules. Cross-tolerance was explored by repeated injections of heroin. Naltrexone action is studied using the methods described above. Repeated injections of heroin at various naltrexone dosages and at various time distances from the last naltrexone dose define the duration of effective antagonist action.